8j86

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'''Unreleased structure'''
 
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The entry 8j86 is ON HOLD until Paper Publication
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==Monkeypox virus DNA replication holoenzyme F8, A22 and E4 complex in a DNA binding form==
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<StructureSection load='8j86' size='340' side='right'caption='[[8j86]], [[Resolution|resolution]] 3.22&Aring;' scene=''>
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== Structural highlights ==
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<table><tr><td colspan='2'>[[8j86]] is a 5 chain structure with sequence from [https://en.wikipedia.org/wiki/DNA_molecule DNA molecule] and [https://en.wikipedia.org/wiki/Monkeypox_virus Monkeypox virus]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=8J86 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=8J86 FirstGlance]. <br>
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</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">Electron Microscopy, [[Resolution|Resolution]] 3.22&#8491;</td></tr>
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<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=CA:CALCIUM+ION'>CA</scene></td></tr>
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<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=8j86 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=8j86 OCA], [https://pdbe.org/8j86 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=8j86 RCSB], [https://www.ebi.ac.uk/pdbsum/8j86 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=8j86 ProSAT]</span></td></tr>
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</table>
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== Function ==
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[https://www.uniprot.org/uniprot/Q5IXW8_MONPV Q5IXW8_MONPV]
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<div style="background-color:#fffaf0;">
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== Publication Abstract from PubMed ==
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Mpox virus has wildly spread over 108 non-endemic regions in the world since May 2022. DNA replication of mpox is performed by DNA polymerase machinery F8-A22-E4, which is known as a great drug target. Brincidofovir and cidofovir are reported to have broad-spectrum antiviral activity against poxviruses, including mpox virus in animal models. However, the molecular mechanism is not understood. Here we report cryogenic electron microscopy structures of mpox viral F8-A22-E4 in complex with a DNA duplex, or dCTP and the DNA duplex, or cidofovir diphosphate and the DNA duplex at resolution of 3.22, 2.98 and 2.79 A, respectively. Our structural work and DNA replication inhibition assays reveal that cidofovir diphosphate is located at the dCTP binding position with a different conformation to compete with dCTP to incorporate into the DNA and inhibit DNA synthesis. Conformation of both F8-A22-E4 and DNA is changed from the pre-dNTP binding state to DNA synthesizing state after dCTP or cidofovir diphosphate is bound, suggesting a coupling mechanism. This work provides the structural basis of DNA synthesis inhibition by brincidofovir and cidofovir, providing a rational strategy for new therapeutical development for mpox virus and other pox viruses.
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Authors:
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Structural basis of human mpox viral DNA replication inhibition by brincidofovir and cidofovir.,Xu Y, Wu Y, Wu X, Zhang Y, Yang Y, Li D, Yang B, Gao K, Zhang Z, Dong C Int J Biol Macromol. 2024 Jun;270(Pt 2):132231. doi: , 10.1016/j.ijbiomac.2024.132231. Epub 2024 May 10. PMID:38735603<ref>PMID:38735603</ref>
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Description:
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From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
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[[Category: Unreleased Structures]]
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</div>
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<div class="pdbe-citations 8j86" style="background-color:#fffaf0;"></div>
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== References ==
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<references/>
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__TOC__
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</StructureSection>
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[[Category: DNA molecule]]
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[[Category: Large Structures]]
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[[Category: Monkeypox virus]]
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[[Category: Dong C]]
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[[Category: Gao K]]
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[[Category: Li D]]
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[[Category: Wu X]]
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[[Category: Wu Y]]
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[[Category: Xu Y]]
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[[Category: Yang B]]
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[[Category: Yang Y]]
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[[Category: Zhang Y]]
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[[Category: Zhang Z]]

Current revision

Monkeypox virus DNA replication holoenzyme F8, A22 and E4 complex in a DNA binding form

PDB ID 8j86

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OCA

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